Fabrication and characterization of UV-emitting nanoparticles as novel radiation sensitizers targeting hypoxic tumor cells.
Fabrication and characterization of UV-emitting nanoparticles as novel radiation sensitizers targeting hypoxic tumor cells.
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DOI：
10.1016/j.optmat.2018.04.033
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发表时间：
2018-06
影响因子：
3.9
通讯作者：
M. Squillante;T. Jüstel;R. Anderson;C. Brecher;Daniel Chartier;J. Christian;Nicholas Cicchetti;S. Espinoza;D. McAdams;Matthias Müller;Brooke Tornifoglio;Yimin Wang;M. Purschke
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文献类型：
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作者：
M. Squillante;T. Jüstel;R. Anderson;C. Brecher;Daniel Chartier;J. Christian;Nicholas Cicchetti;S. Espinoza;D. McAdams;Matthias Müller;Brooke Tornifoglio;Yimin Wang;M. Purschke
放射治疗是治疗癌症的主要治疗技术之一，近三分之二的癌症患者接受放射治疗。尽管放射疗法在杀死癌细胞方面非常有效，但与其他形式的癌症治疗一样，放射疗法难以处理实体瘤内的缺氧区域。癌细胞的不完全杀死可能导致复发和复发。此处介绍的研究正在研究通过使用发射紫外线光子的闪烁纳米颗粒来增强放射治疗的功效。波长在 230nm 至 280nm 之间的紫外线光子由于与 DNA 直接相互作用而能够使细胞失活，从而造成多种形式的损伤。发射紫外线的纳米粒子将以两种方式增强治疗效果：首先，在癌细胞附近产生紫外线光子，导致直接且不依赖于氧气的 DNA 损伤；其次，将所施加的较高能量 X 射线下转换为更柔和的 X 射线和粒子，以便在目标肿瘤区域中更有效地吸收。最终结果将是纳米粒子在治疗肿瘤缺氧细胞方面具有更高的功效，满足重要的、未满足的临床需求。我们的初步实验表明，使用闪烁的 LuPO4:Pr 纳米粒子比单独使用初级辐射所实现的细胞死亡增加。这项工作描述了纳米颗粒的制造、它们的物理表征以及紫外发射的光谱表征。这项工作还提供了体外结果，证明 X 射线杀死细胞的功效增强，并且纳米颗粒的非特异性毒性较低。
Radiation therapy is one of the primary therapeutic techniques for treating cancer, administered to nearly two-thirds of all cancer patients. Although largely effective in killing cancer cells, radiation therapy, like other forms of cancer treatment, has difficulty dealing with hypoxic regions within solid tumors. The incomplete killing of cancer cells can lead to recurrence and relapse.The research presented here is investigating the enhancement of the efficacy of radiation therapy by using scintillating nanoparticles that emit UV photons. UV photons, with wavelengths between 230 nm and 280 nm, are able to inactivate cells due to their direct interaction with DNA, causing a variety of forms of damage. UV-emitting nanoparticles will enhance the treatment in two ways: first by generating UV photons in the immediate vicinity of cancer cells, leading to direct and oxygen-independent DNA damage, and second by down-converting the applied higher energy X-rays into softer X-rays and particles that are more efficiently absorbed in the targeted tumor region. The end result will be nanoparticles with a higher efficacy in the treatment of hypoxic cells in the tumor, filling an important, unmet clinical need.Our preliminary experiments show an increase in cell death using scintillating LuPO4:Pr nanoparticles over that achieved by the primary radiation alone. This work describes the fabrication of the nanoparticles, their physical characterization, and the spectroscopic characterization of the UV emission. The work also presentsin vitroresults that demonstrate an enhanced efficacy of cell killing with x-rays and a low unspecific toxicity of the nanoparticles.